Parkinsonism as a Potential Neurologic Immune-Mediated Adverse Event of Immune Checkpoint Inhibitors

OBJECTIVES: Immune checkpoint inhibitor (ICI)-related parkinsonism is an exceedingly rare neurologic immune-related adverse event (irAE). METHODS: We reviewed retrospectively the French Pharmacovigilance Agency and French National Center for Autoimmune Encephalitis and Paraneoplastic Neurologic Syndromes Lyon databases (2015-2025) following identification of index case. RESULTS: We identified 4 male and one female patient, with a median age of 67 years (range 34-75), who developed acute-to-subacute parkinsonism after a median of 4 ICI cycles (range 1-12). The predominant phenotype was bilateral akinetic-rigid syndrome (rigidity n = 5, bradykinesia n = 4, tremor n = 3); the median modified Rankin Scale score at onset was 3. CSF analysis showed pleocytosis in 2/4 tested patients and elevated protein in 4/4 tested patients. Dopamine transporter imaging demonstrated bilateral dopaminergic denervation in both patients tested (n = 2), with documented reversibility in one. ICI discontinuation alone (n = 1/2) or combined with immunomodulatory therapy (n = 3) yielded clinical improvement over a median follow-up of 15 months (range 3-30). Levodopa/carbidopa supplementation was required in 2 patients. DISCUSSION: Post-ICI-related parkinsonism is a rare but potentially reversible irAE. Early recognition and prompt ICI discontinuation may favor significant clinical recovery. Immunosuppressive therapy should be considered for severe cases or those not improving after ICI discontinuation alone.